Growing out of depression

For decades, people suffering from mood disorders have found relief with antidepressants, but the biological basis for the action of these highly prescribed medications remains unclear. One theory, based on landmark studies by Ronald S. Duman, Ph.D., the Elizabeth House and Jameson Mears Professor of Psychiatry, proposes that these drugs exert their effects by stimulating neuronal growth factors; these proteins generate new nerve cells in certain brain areas that lead to changes in mood and behavior.

With Jennifer Warner-Schmidt, Ph.D., a former graduate student now at Rockefeller University, Duman has identified vascular endothelial growth factor, or VEGF, as one such protein.

In the March 13 issue of the Proceedings of the National Academy of Sciences, the team reports that VEGF is produced in the brain’s hippocampal region following administration of various antidepressants. Higher VEGF levels led to increased cell division and positive behavioral responses in well-established rat models of depression. Conversely, blocking VEGF action inhibited these effects.

These findings point to the VEGF pathway as a possible target in the development of new and better antidepressant drugs.